FDA Approves Gene Therapy

Spark Therapeutics’ Luxturna is for the treatment of patients with the rare genetic retinal disease Leber congenital amaurosis.

The US Food and Drug Administration (FDA) approved  the 3rd gene therapy of 2017. The first two - Kymriah ( tisagenlecleucel) from Novartis Pharmaceuticals and Yescarta (axicabtagene ciloleucel) from Kite Pharma – are chimeric antigen receptor (CAR) T-cell therapies for the treatment of cancer (B-cell precursor acute lymphoblastic leukemia and relapsed or refractory large B-cell lymphoma, respectively). Luxturna (voretigene neparvovec-rzyl) from Spark Therapeutics is different. It is the first directly administered gene therapy approved in the U.S. that targets a disease caused by mutations in a specific gene. Luxturna is for patients with an inherited form of vision loss that may result in blindness - Leber congenital amaurosis. It is a treatment specifically for adults and children with a mutated RPE65 gene, which is key to the production of an enzyme required for normal vision.

Hereditary retinal dystrophies are a broad group of genetic retinal disorders that are associated with progressive visual dysfunction and are caused by mutations in any one of more than 220 different genes, according to FDA. In the US, approximately 1,000 to 2,000 people suffer from biallelic RPE65 mutation-associated retinal dystrophy. The disease is passed on to children when both parents contribute mutated genes, although the mutations do not need to be the same. When the RPE65 gene is affected by mutations, the RPE65 activity can be reduced or missing, which interrupts the visual cycle. Typically vision declines over time and eventually results in total blindness.

When treated with the new gene therapy, patients received non-mutated copies of the RPE65 in their retinal cells via subretinal injection. The treated cells then produce the protein that mediates the reaction to convert light into electrical signals. A naturally occurring adeno-associated virus is used to deliver the gene.

“The approval of Luxturna further opens the door to the potential of gene therapies,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER). “Patients with biallelic RPE65 mutation-associated retinal dystrophy now have a chance for improved vision, where little hope previously existed.”

FDA Commissioner Scott Gottlieb also noted that the approval of Luxturna “marks another first in the field of gene therapy — both in how the therapy works and in expanding the use of gene therapy beyond the treatment of cancer to the treatment of vision loss — and this milestone reinforces the potential of this breakthrough approach in treating a wide-range of challenging diseases. The culmination of decades of research has resulted in three gene therapy approvals this year for patients with serious and rare diseases. I believe gene therapy will become a mainstay in treating, and maybe curing, many of our most devastating and intractable illnesses.”

In 2018, FDA will be issuing “a suite of disease-specific guidance documents on the development of specific gene therapy products to lay out modern and more efficient parameters — including new clinical measures — for the evaluation and review of gene therapy for different high-priority diseases where the platform is being targeted,” Gottlieb said.


Nigel Walker

Mr. Walker is the founder and managing director of That’s Nice LLC, a research-driven marketing agency with 20 years dedicated to life sciences. Nigel harnesses the strategic capabilities of Nice Insight, the research arm of That’s Nice, to help companies communicate science-based visions to grow their businesses. Mr. Walker earned a bachelor’s degree in graphic design with honors from London College.